Voluntary sustainability standards could significantly reduce detrimental impacts of global agriculture.

Voluntary sustainability standards (VSS) are stakeholder-derived principles with measurable and enforceable criteria to promote sustainable production outcomes. While institutional commitments to use VSS to meet sustainable procurement policies have grown rapidly over the past decade, we still have relatively little understanding of the (i) direct environmental benefits of large-scale VSS adoption; (ii) potential perverse indirect impacts of adoption; and (iii) implementation pathways. Here, we illustrate and address these knowledge gaps using an ecosystem service modeling and scenario analysis of Bonsucro, the leading VSS for sugarcane. We find that global compliance with the Bonsucro environmental standards would reduce current sugarcane production area (-24%), net tonnage (-11%), irrigation water use (-65%), nutrient loading (-34%), and greenhouse gas emissions from cultivation (-51%). Under a scenario of doubled global sugarcane production, Bonsucro adoption would further limit water use and greenhouse gas emissions by preventing sugarcane expansion into water-stressed and high-carbon stock ecosystems. This outcome was achieved via expansion largely on existing agricultural lands. However, displacement of other crops could drive detrimental impacts from indirect land use. We find that over half of the potential direct environmental benefits of Bonsucro standards under the doubling scenario could be achieved by targeting adoption in just 10% of global sugarcane production areas. However, designing policy that generates the most environmentally beneficial Bonsucro adoption pathway requires a better understanding of the economic and social costs of VSS adoption. Finally, we suggest research directions to advance sustainable consumption and production.

Corticostriatal circuit defects in Hoxb8 mutant mice.

Hoxb8 mutant mice exhibit compulsive grooming and hair removal dysfunction similar to humans with the obsessive-compulsive disorder (OCD)-spectrum disorder, trichotillomania. As, in the mouse brain, the only detectable cells that label with Hoxb8 cell lineage appear to be microglia, we suggested that defective microglia cause the neuropsychiatric disorder. Does the Hoxb8 mutation in microglia lead to neural circuit dysfunctions? We demonstrate that Hoxb8 mutants contain corticostriatal circuit defects. Golgi staining, ultra-structural and electrophysiological studies of mutants reveal excess dendritic spines, pre- and postsynaptic structural defects, long-term potentiation and miniature postsynaptic current defects. Hoxb8 mutants also exhibit hyperanxiety and social behavioral deficits similar to mice with neuronal mutations in Sapap3, Slitrk5 and Shank3, reported models of OCD and autism spectrum disorders (ASDs). Long-term treatment of Hoxb8 mutants with fluoxetine, a serotonin reuptake inhibitor, reduces excessive grooming, hyperanxiety and social behavioral impairments. These studies provide linkage between the neuronal defects induced by defective Hoxb8-microglia and neuronal dysfunctions directly generated by mutations in synaptic components that result in mice, which display similar pathological grooming, hyperanxiety and social impairment deficits. Our results shed light on Hoxb8 microglia-driven circuit-specific defects and therapeutic approaches that will become essential to developing novel therapies for neuropsychiatric diseases such as OCD and ASDs with Hoxb8-microglia being the central target.

Corticostriatal circuit defects in Hoxb8 mutant mice.

This corrects the article DOI: 10.1038/mp.2017.180.

Risk factors for dysphagia after a spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To determine the risk factors predictive of dysphagia after a spinal cord injury (SCI). SETTING: None. METHODS: A comprehensive literature search was performed in five scientific databases for English articles that identified risk factors for dysphagia after a SCI in adult (≥19 years) individuals. Data extracted included: author name, year and country of publication, participant demographics, sample size, study design, method of dysphagia diagnosis, and risk factor percentages. Methodological quality of studies was assessed using the Newcastle-Ottawa Scale. For identified risk factors, risk percentages were transformed into risk ratios (RR) with 95% confidence intervals. Quantitative synthesis was performed for risk factors reported in two or more studies using restricted maximum-likelihood estimator random effects models. RESULTS: Eleven studies met inclusion criteria of which ten studies were of moderate quality (n = 10). Significant risk factors included: age, injury severity, level of injury, presence of tracheostomy, coughing, voice quality, bronchoscopy need, pneumonia, mechanical ventilation, nasogastric tubes, comorbid injury, and a cervical surgery. Results of the quantitative synthesis indicated that the presence of a tracheostomy posed a threefold greater risk of the development of dysphagia (RR: 3.67); while, cervical surgery posed a 1.3 times greater risk of the development of dysphagia (RR: 1.30). CONCLUSIONS: Knowledge of these risk factors can be a resource for clinicians in the early diagnosis and appropriate medical management of dysphagia post SCI.

Saprolegnia diclina IIIA and S. parasitica employ different infection strategies when colonizing eggs of Atlantic salmon, Salmo salar L.

Here, we address the morphological changes of eyed eggs of Atlantic salmon, Salmo salar L. infected with Saprolegnia from a commercial hatchery and after experimental infection. Eyed eggs infected with Saprolegnia spp. from 10 Atlantic salmon females were obtained. Egg pathology was investigated by light and scanning electron microscopy. Eggs from six of ten females were infected with S. parasitica, and two females had infections with S. diclina clade IIIA; two Saprolegnia isolates remained unidentified. Light microscopy showed S. diclina infection resulted in the chorion in some areas being completely destroyed, whereas eggs infected with S. parasitica had an apparently intact chorion with hyphae growing within or beneath the chorion. The same contrasting pathology was found in experimentally infected eggs. Scanning electron microscopy revealed that S. parasitica grew on the egg surface and hyphae were found penetrating the chorion of the egg, and re-emerging on the surface away from the infection site. The two Saprolegnia species employ different infection strategies when colonizing salmon eggs. Saprolegnia diclina infection results in chorion destruction, while S. parasitica penetrates intact chorion. We discuss the possibility these infection mechanisms representing a necrotrophic (S. diclina) vs. a facultative biotrophic strategy (S. parasitica).

A thicker chorion gives ova of Atlantic salmon (Salmo salar L.) the upper hand against Saprolegnia infections.

Since the ban of malachite green in the fish farming industry, finding alternative ways of controlling Saprolegnia infections has become of utmost importance. Much effort has been made to elucidate the mechanisms by which Saprolegnia invades fish eggs. Little is known about the defence mechanisms of the hosts, making some eggs more prone to infection than others. One clue might lie in the composition of the eggs. As the immune system in the embryos is not developed yet, the difference in infection levels could be explained by factors influenced by the mother herself, by either transferring passive immunity, influencing the physical aspects of the eggs or both. One of the physical aspects that could be influenced by the female is the chorion, the extracellular coat surrounding the fish egg, which is in fact the first major barrier to be overcome by Saprolegnia spp. Our results suggest that a thicker chorion in eggs from Atlantic salmon gives a better protection against Saprolegnia spp. In addition to the identification of differences in sensitivity of eggs in a fish farm set-up, we were able to confirm these results in a laboratory-controlled challenge experiment.

Protein biosensing with fluorescent microcapillaries.

Capillaries with a high-index fluorescent coating represent a new type of whispering-gallery-mode (WGM) microcavity sensor. By coating silicon quantum dots (Si-QDs) onto the channel wall of a microcapillary, a cylindrical microcavity forms in which the optical confinement arises from the index contrast at the interface between the QD layer and the glass capillary wall. However, the ability to functionalize the QD layer for biosensing applications is an open question, since the layer consists of a mixture of Si-QDs embedded in a glassy SiOx matrix. Here, we employ a polyelectrolyte (PE) multilayer approach to functionalize the microcapillary inner surface and demonstrate the potential of this refractive index sensing platform for label-free biosensing applications, using biotin-neutravidin as a specific interaction model.

A large colonial choanoflagellate from Mono Lake harbors live bacteria.

As the closest living relatives of animals, choanoflagellates offer insights into the ancestry of animal cell physiology. Here, we report the isolation and characterization of a colonial choanoflagellate from Mono Lake, California. The choanoflagellate forms large spherical colonies that are an order of magnitude larger than those formed by the closely related choanoflagellate Salpingoeca rosetta. In cultures maintained in the laboratory, the lumen of the spherical colony is filled with a branched network of extracellular matrix and colonized by bacteria, including diverse Gammaproteobacteria and Alphaproteobacteria. We propose to erect Barroeca monosierra gen. nov., sp. nov. Hake, Burkhardt, Richter, and King to accommodate this extremophile choanoflagellate. The physical association between bacteria and B. monosierra in culture presents a new experimental model for investigating interactions among bacteria and eukaryotes. Future work will investigate the nature of these interactions in wild populations and the mechanisms underpinning the colonization of B. monosierra spheres by bacteria. IMPORTANCE: The diversity of organisms that live in the extreme environment of Mono Lake (California, USA) is limited. We sought to investigate whether the closest living relatives of animals, the choanoflagellates, exist in Mono Lake, a hypersaline, alkaline, arsenic-rich environment. We repeatedly isolated members of a new species of choanoflagellate, which we have named Barroeca monosierra. Characterization of B. monosierra revealed that it forms large spherical colonies containing diverse co-isolated bacteria, providing an opportunity to investigate mechanisms underlying physical associations between eukaryotes and bacteria.

Distinct spatiotemporal roles of hedgehog signalling during chick and mouse cranial base and axial skeleton development.

The cranial base exerts a supportive role for the brain and includes the occipital, sphenoid and ethmoid bones that arise from cartilaginous precursors in the early embryo. As the occipital bone and the posterior part of the sphenoid are mesoderm derivatives that arise in close proximity to the notochord and floor plate, it has been assumed that their development, like the axial skeleton, is dependent on Sonic hedgehog (Shh) and modulation of bone morphogenetic protein (Bmp) signalling. Here we examined the development of the cranial base in chick and mouse embryos to compare the molecular signals that are required for chondrogenic induction in the trunk and head. We found that Shh signalling is required but the molecular network controlling cranial base development is distinct from that in the trunk. In the absence of Shh, the presumptive cranial base did not undergo chondrogenic commitment as determined by the loss of Sox9 expression and there was a decrease in cell survival. In contrast, induction of the otic capsule occurred normally demonstrating that induction of the cranial base is uncoupled from formation of the sensory capsules. Lastly, we found that the early cranial mesoderm is refractory to Shh signalling, likely accounting for why development of the cranial base occurs after the axial skeleton. Our data reveal that cranial and axial skeletal induction is controlled by conserved, yet spatiotemporally distinct mechanisms that co-ordinate development of the cranial base with that of the cranial musculature and the pharyngeal arches.

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics.

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox® model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity.

The role of 'public opinion' in the UK animal research debate.

Animal research remains a deeply controversial topic in biomedical science. While a vast amount has been written about the ethical status of laboratory animals, far less academic attention has been devoted to the public and, more specifically, to public opinion. Rather than what the public think, this article considers the role of 'public opinion'. It draws on a recent empirical study which involved interviews with laboratory scientists who use animals in their research, and with other UK stakeholders. The first section of the paper demonstrates that public opinion has become a kind of resource in the animal research debate. Public opinion polls, in particular, are frequently cited. The second section explores this further and argues that, for all sides, appealing to public opinion is a key way to show legitimacy. Finally, the paper shifts gear to consider whether public opinion should matter, both for ethical reasoning and for science policy.

Identification of synergistic signals initiating inner ear development.

Tissue manipulation experiments in amphibians more than 50 years ago showed that induction of the inner ear requires two signals: a mesodermal signal followed by a neural signal. However, the molecules mediating this process have remained elusive. We present evidence for mesodermal initiation of otic development in higher vertebrates and show that the mesoderm can direct terminal differentiation of the inner ear in rostral ectoderm. Furthermore, we demonstrate the synergistic interactions of the extracellular polypeptide ligands FGF-19 and Wnt-8c as mediators of mesodermal and neural signals, respectively, initiating inner ear development.

Paenibacillus polymyxa antagonizes oomycete plant pathogens Phytophthora palmivora and Pythium aphanidermatum.

AIM: To find sustainable alternatives to the application of synthetic chemicals for oomycete pathogen suppression. METHODS AND RESULTS: Here, we present experiments on an Arabidopsis thaliana model system in which we studied the antagonistic properties of rhizobacterium Paenibacillus polymyxa strains towards the oomycete plant pathogens Phytophthora palmivora and Pythium aphanidermatum. We carried out studies on agar plates, in liquid media and in soil. Our results indicate that P. polymyxa strains significantly reduced P. aphanidermatum and P. palmivora colonization in liquid assays. Most plants that had been treated with P. polymyxa survived the P. aphanidermatum inoculations in soil assays. CONCLUSIONS: The antagonistic abilities of both systems correlated well with mycoidal substance production and not with the production of antagonistic substances from the biocontrol bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Our experiments highlight the need to take biofilm formation and niche exclusion mechanisms into consideration for biocontrol assays performed under natural conditions.

Use of low dose tacrolimus, mycophenolate mofetil and maintenance IL-2 receptor blockade in an islet transplant recipient.

The utilization of dual maintenance therapy with tacrolimus and sirolimus (the Edmonton protocol) has been widely adopted as standard immunosuppression for islet cell transplantation. This immunosuppression regimen has numerous toxicities including renal dysfunction, anemia, and recurrent aphthous ulcers. We present a case of a 63-yr-old Caucasian female who received an isolated islet transplant. Over the first six months post-transplant, the patient developed severe anemia, intractable aphthous ulcers, and renal dysfunction. Islet transplant function was excellent and the patient is insulin-independent since the end of the second month post-transplant. However, because of the above toxicities, a decision was made to change her immunosuppression regimen eight months post-transplant to low dose tacrolimus, mycophenolate mofetil, and a monthly maintenance infusion of daclizumab. Since then, her aphthous ulcers have disappeared, renal function has improved, and islet cell function remains stable.

Use of high-dose ganciclovir for a resistant cytomegalovirus infection due to UL97 mutation.

Cytomegalovirus (CMV) infection is a major complication following solid organ transplantation resulting in significant morbidity and mortality. The guidelines published in 2004 have recommendations for therapy; however, the frequency of resistant CMV infection is increasing and therapy is not clearly defined. There are a few alternatives to ganciclovir such as foscarnet, cidofovir, and leflunomide; however, their use is limited by adverse effects. This report summarizes the successful use of high-dose ganciclovir for the treatment of a resistant CMV caused by UL97 mutation.

Pregnancy outcomes of women with pruritus, normal bile salts and liver enzymes: a case control study.

BACKGROUND: Obstetric cholestasis (OC) is associated with increased maternal and perinatal complications. Nevertheless, data on pregnancy outcomes of women who experience pruritus on a transient basis, but have normal bile salts and liver function tests (LFT) is scarce. METHODS: The maternal and fetal outcomes of 144 women with pruritus but normal bile salts and LFTs were compared with the next delivered patient without itch who matched for age, ethnicity and parity. RESULTS: The study and control groups had similar mean gestational ages at delivery and birth weights (p>0.05, t test). However, women with pruritus were more likely to have meconium-stained liqor, abnormal intrapartum cardiotocography and postpartum hemorrhage (PPH) (p<0.05, Fisher's exact test). There appears to be a trend towards a higher rate of instrumental delivery (p=0.07) in the study compared to the control group, although this did not reach statistical significance. CONCLUSION: This study suggests that women who have transient pruritus with normal bile salts and liver biochemistry appear to have higher intrapartum and postpartum complications and require increased vigilance. In order to evaluate this finding, further prospective studies will be required.

Antagonistic interactions between the flavonoids hesperetin and naringenin and beta-lactam antibiotics against Staphylococcus aureus.

Flavonoids are a group of polyphenolic plant compounds with a range of biological activities. This study shows that the flavonoids hesperetin and naringenin have antibacterial activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates. Minimum inhibitory concentrations for hesperetin were 250 and 500 microg/mL, respectively, and for naringenin were 125 and 250 microg/mL, respectively. This effect was reversed by the beta-lactam antibiotics methicillin, penicillin and oxacillin, but not by cefoxitin. For bacteria growing in the presence of these antibiotics, the flavonoids had no effect on the levels of beta-lactamase enzymes and PBP-2' compared to controls. Electron microscopy showed abnormal morphology in bacteria treated with subinhibitory concentrations of flavonoids. These results are interesting because previous studies have reported synergistic interactions between flavonoids and beta-lactam antibiotics. It is suggested that an interaction removes both inhibitors from the bacterial growth milieu.

AFM capabilities in characterization of particles and surfaces: from angstroms to microns.

Scanning probe microscopy (SPM), invented 25 years ago, is now routinely employed as a surface characterization technique. Atomic force microscopy (AFM) is the most widely used form of SPM, since AFM can be used in ambient conditions with minimal sample preparation. Examples of applications relevant to cosmetics include, but are not limited to, hair and skin roughness measurements and powder particle and nano-emulsion characterization. AFM is well suited for individual particle characterization, especially for measurements of volume, height, size, shape, aspect ratio, and particle surface morphology. Statistical distributions for a large set of particles can be generated through single-particle analysis techniques (i.e., ensemble-like information). AFM is better capable of resolving complex particle-size distributions than dynamic light-scattering (DLS). Single-particle analysis techniques with AFM can be more cost- and time-effective than analyses using scanning electron microscopy (SEM). However, AFM offers resolution that is comparable to or greater than SEM or transmission electron microscopy (TEM) and routinely allows direct measurements of the particle height and volume and produces images easily displayed in a quantified 3D format.

Differential contribution of kainate receptors to excitatory postsynaptic currents in superficial layer neurons of the rat medial entorhinal cortex.

Although in situ hybridization studies have revealed the presence of kainate receptor (KAR) mRNA in neurons of the rat medial entorhinal cortex (mEC), the functional presence and roles of these receptors are only beginning to be examined. To address this deficiency, whole cell voltage clamp recordings of locally evoked excitatory postsynaptic currents (EPSCs) were made from mEC layer II and III neurons in combined entorhinal cortex-hippocampal brain slices. Three types of neurons were identified by their electroresponsive membrane properties, locations, and morphologies: stellate-like "Sag" neurons in layer II (S), pyramidal-like "No Sag" neurons in layer III (NS), and "Intermediate Sag" neurons with varied morphologies and locations (IS). Non-NMDA EPSCs in these neurons were composed of two components, and the slow decay component in NS neurons had larger amplitudes and contributed more to the combined EPSC than did those observed in S and IS neurons. This slow component was mediated by KARs and was characterized by its resistance to either 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466, 100 microM) or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[lsqb]f[rsqb]quinoxaline-7-sulfonamide (NBQX, 1 microM), relatively slow decay kinetics, and sensitivity to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-50 microM). KAR-mediated EPSCs in pyramidal-like NS neurons contributed significantly more to the combined non-NMDA EPSC than did those from S and IS neurons. Layer III neurons of the mEC are selectively susceptible to degeneration in human temporal lobe epilepsy (TLE) and animal models of TLE such as kainate-induced status epilepticus. Characterizing differences in the complement of postsynaptic receptors expressed in injury prone versus injury resistant mEC neurons represents an important step toward understanding the vulnerability of layer III neurons seen in TLE.

Resistance of nicotiana benthamiana to phytophthora infestans is mediated by the recognition of the elicitor protein INF1

Phytophthora infestans, the agent of potato and tomato late blight disease, produces a 10-kD extracellular protein, INF1 elicitin. INF1 induces a hypersensitive response in a restricted number of plants, particularly those of the genus Nicotiana. In virulence assays with different P. infestans isolates, five Nicotiana species displayed resistance responses. In all of the interactions, after inoculation with P. infestans zoospores, penetration of an epidermal cell was observed, followed by localized necrosis typical of a hypersensitive response. To determine whether INF1 functions as an avirulence factor in these interactions, we adopted a gene-silencing strategy to inhibit INF1 production. Several transformants deficient in inf1 mRNA and INF1 protein were obtained. These strains remained pathogenic on host plants. However, in contrast to the wild-type and control transformant strains, INF1-deficient strains induced disease lesions when inoculated on N. benthamiana. These results demonstrate that the elicitin INF1 functions as an avirulence factor in the interaction between N. benthamiana and P. infestans.